(S)-3-hydroxypyrrolidine represented by the following Formula 1 is a very important compound in preparing pharmaceutical products, which has been widely used as a major chiral intermediate for pharmaceutical products commercially available on the market and new pharmaceutical products under clinical tests, and thus, there have been many studies thereon.

Examples in which (S)-3-hydroxypyrrolidine represented by Formula 1 are actually used in preparing pharmaceutical products are as follows: a major intermediate raw material of a calcium antagonist (Barnidipine) (European Patent Laid-Open Publication No. 160,451; J. Med. Chem. 1986, 29, 2504˜2511; Japanese Patent Laid-Open Publication No. (Sho) 61-267577; Japanese Patent Laid-Open Publication No. (Sho) 61-63652); carbapenem antibiotics (Heterocycles, vol 24, No 5, 1986; Tetrahedron Lett., 25, 2793, 1984; International Publication No. WO88/08845; J. Org. Chem. 1992, 57, 4352˜4361); quinolone-based antibiotics (U.S. Pat. No. 4,916,141; European Patent Laid-Open Publication No. 391,169; European Patent laid-Open Publication No. 304,087), analgesics (κ-receptor agonists) (European Patent Laid-Open Publication Nos. 398,720 and 366,327; J. Med. Chem., 1994, 37, 2138˜2144), and a major intermediate raw material of a neurotransmitter (International Publication No. WO01/19817). That is, (S)-3-hydroxypyrrolidine is used as a major substance for preparation of various chiral pharmaceutical products in a wide range of application fields.
Conventional techniques related to preparation of optically pure (S)-3-hydroxypyrrolidine, which is useful as a major intermediate for preparation of chiral compounds described above, will be described below.
For example, a method of preparing 3-(R)-hydroxypyrrolidine in a single step reaction involving decarboxylation using (R)-3-hydroxy-L-proline as a starting material is disclosed (JP2001220372; WO97/43256; JP05255204; Synlett, 1995, 55-57; Syn. Comm. 1994, 24, 1381˜1387; Korean J. of Med. Chem. 1993, 3, 72˜80; Syn. Comm. 1993, 23, 2691˜2699; J. Chem. Soc. Perkin Trans. 1. 1993, 1421˜1424; Bioorganic & Medicinal Chemistry Letters, 2, 827). However, in case of 3-(R)-hydroxypyrrolidine, the starting material, (R)-3-hydroxy-L-proline, is very expensive and thus is difficult to be applied to mass production.
A method of obtaining (S)-3-hydroxypyrrolidine through several steps using D-malic acid as a raw material is known (Syn. Commun. 15, 587˜598, 1985; J. Med. Chem. 1994, 37, 2138˜2144). However, this technique has a disadvantage of multiple steps being involved and also has problems in that LiAlH4 or B2H6 used as a reduction agent is expensive and difficult to industrially handle. Further, since D-malic acid is expensive and is not mass-produced, this method is not an economical preparation method.
Recently, a new synthetic method that comprises an epoxy ring-opening reaction by way of amine of 3,4-epoxy-1-butanol followed by 5-cyclization (WO2003/097594) has been reported. However, this method has a disadvantage in that raw materials are expensive. Further, synthesis of (S)-3-hydroxypyrrolidine and derivatives thereof through activation of a hydroxyl group followed by double substitution of amine, by using 1,2,4-trihydroxybutane, which is a derivative of 3,4-epoxy-1-butanol, as a starting material has been reported (WO2000/015610). However, this method also suffers from a problem that raw materials are expensive.
As for similar methods, there has been known a synthetic method using a derivative of a 3,4-dihydroxy-1-butanol (JP60104061); a synthetic method using 3,4-dihydroxy-1-butylamine (JP57056457); and a synthetic method comprising cyan group substitution and cyan group reduction followed by cyclization, using 3-chloro-1,2-propandiol and derivatives thereof (EP431,521 and EP347,818). However, these preparation methods also have a problem in that it is difficult to industrially supply raw materials.
Therefore, there is a need for development of a method of preparing (S)-3-hydroxypyrrolidine using an inexpensive, optically active raw material as a starting material so that it can be industrially mass-produced.